Hemodialysis (HD) and peritoneal dialysis (PD) are methods of removing toxic substances (impurities or wastes) from the blood when the kidneys are unable to do so sufficiently. Dialysis is most frequently used for patients who have kidney failure, but may also be used to quickly remove drugs or poisons in acute situations. This technique can be life saving in people with acute or chronic kidney failure. Best known is hemodialysis, which works by circulating the blood along special filters outside the body in a dialysis machine. Here, the blood flows across a semi-permeable membrane (the dialyser or filter), on the other side of which flows a dialysis fluid in a counter-current direction to the blood flow. The dialysing membrane allows passage of substances below a certain molecular cut-off. By diffusion the concentration of these substances will end up being the same on both sides of the membrane. The dialysis fluid removes the toxins from the blood and is generally discarded as waste dialysate. The chemical imbalances and impurities of the blood are being brought back in minimal balance and the blood is then returned to the body. The efficacy of hemodialysis is 10-15%, which means that 10-15% of the toxins are being removed from the blood. Typically, most patients undergo hemodialysis for three sessions every week. Each session lasts normally 3-4 hours. This is very inconvenient, and the physical and social side effects of dialysis to the patients are a great concern.
In order to provide for portable dialysis devices, that will allow patients to engage in normal daily activities, artificial kidneys have been developed. Essentially there are two types of artificial kidneys.
In one form, the principle of the artificial kidney consists of extracting urea and other more toxic middle molecules from blood by dialysis and regeneration of the dialysate by means of an adsorbent, usually activated carbon. In the case of a system based on such a dialysis kidney machine, a key aspect resides in regenerating the dialysis fluid when the latter is to be recycled into the dialyser. Dialysis kidney machines that can be encountered in the prior art include for instance those described in GB1406133, and US 2003/0097086. GB1406133 discloses an artificial kidney of the recycle type having an improved adsorbent comprising activated carbon and alumina. US 2003/0097086 discloses a portable dialysis device comprising dialyzers connected in series that utilize dialysate, and further comprising a plurality of contoured sorbent devices, which are connected in series and are for regenerating the spent dialysate. As adsorption materials for regeneration of the spent dialysate, activated charcoal, urease, zirconium phosphate, hydrous zirconium oxide and/or activated carbon are provided.
In another form, the principle of the artificial kidney may be based on ultrafiltration, or hemofiltration, using appropriate membranes, wherein large molecules including blood cells are retained in the retentate on the filter, and the toxic substances are collected in the (ultra)filtrate. During hemofiltration, a patient's blood is passed through a set of tubing (a filtration circuit) via a machine to a semipermeable membrane (the filter) where waste products and water are removed. Replacement fluid is added and the blood is returned to the patient. In a similar fashion to dialysis, hemofiltration involves the movement of solutes across a semi-permeable membrane. However, the membrane used in hemofiltration is far more porous than that used in hemodialysis, and no dialysate is used-instead a positive hydrostatic pressure drives water and solutes across the filter membrane where they are drained away as filtrate. An isotonic replacement fluid is added to the resultant filtered blood to replace fluid volume and valuable electrolytes. This is then returned to the patient. Thus, in the case of ultrafiltration, a key aspect resides in separating the urea from the other components in the ultrafiltrate such as salts which have also passed through the membrane but which must be reincorporated into the blood in order to maintain the electrolyte composition thereof substantially constant.
Another approach relates to electrodialysis, a method to fasten the dialysis process by applying an electrical field over the dialysate membrane similar to electrophoresis systems. For instance in WO03020403 a dialysate system is proposed with an electrical voltage over the membrane. The proposed voltage is in the range of 50-150 Volts. It is claimed that the electrical field promotes the diffusion rate and hereby the clearance rate of toxins such as small solutes, phosphate, creatinine, beta2microglobuline and even urea. A major drawback however is the required high voltage resulting in significant heating of the blood. This system therefore requires an additional cooling section making the system bulky and energy consuming.
Another relevant approach is known from purification of water and is called electrosorption. E.g. in US2007284313 an apparatus is disclosed for removing inorganic ions such as salt and metals from water by means of carbon electrodes that are activated with a small voltage. This system seems to work well for water and inorganic substances. Nothing has been disclosed so far for removing organic molecules and substances such as toxic small and middle molecules and proteins via electrosorption.
In conclusion, the prior art discloses both dialysing and ultrafiltration devices, wherein various substances may be used as sorbents. Also the use of an external electrical field to boost the dialysate diffusion process has been disclosed.
The problem with the system of the prior art is that however, that they are still too large due to limited sorption capacity of the materials, or not efficient or both, in order to allow small, desk-top sized or wearable blood purification systems.
Removing toxins from blood and tissue via electrical activated oxidation has been described already in 1975 e.g. in U.S. Pat. No. 3,878,564. In 1982, in particular U.S. Pat. No. 4,473,449, such a process has been described for the regeneration of dialysate fluid using Pt, Ti with TiO2, SnO2 or RuO2 coatings as electrode materials. This process has never been applied nor practiced in blood purification, most likely because the process produces unwanted oxidation products such as chloramines.
Removing toxins via an electrosorption device has been well described in patent EP2092944 published in 2009. Although the proposed technology is regarded as an important step forward in blood purification, the removal of urea is still problematic and requires a relatively high volume and mass of sorbents. An electrosorption and decomposition system according to the preamble of claim 1 is known from WO2012060700A. This known system combines electrosorption of electrolytes and electrocatalytical decomposition of organic toxins such as urea by means a sorbent unit comprising sorbents and electrodes. This approach has been tested with very good results. However additional safety measures are needed in order to secure the quality of the cleansed fluid, especially with respect to the prevention of oxidative stress. Oxidative stress may occur due to the formation of unwanted byproducts such as chloramines during the electrocatalytic decomposition. Prevention of oxidative stress is paramount for a safe and biocompatible operation.
It is an object of the present invention to overcome the potential problems with oxidative stress and to provide a compact and efficient sorption-filter and decomposition system with inbuilt measures to prevent oxidative stress for use in hemodialysis, peritoneal dialysis systems and—more genericly—for use in blood purification systems such as a wearable artificial kidney, artificial liver, artficial lung etc. In similar form such a system is applicable for purification of other fluids such as the purification of water, waste water treatment and purification of e.g. aquarium water.